Effects of Ghrelin Administration on Motivation

NCT06576440 | Completed

• 1 other identifier: TUE008_ADMIN
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Everyday humans are confronted with a plethora of rewards competing for their attention. Nevertheless, to obtain a goal or reward, humans often need to invest effort. When humans are confronted with the challenge to integrate costs of action such as the effort of walking to one's favorite lunch place with its anticipated benefits (i.e., eating one's favorite meal), accumulating evidence suggest that humans might "go with the gut". Ghrelin is a stomach-derived hormone and the only known circulating peptide that stimulates appetite. At the same time, patients with major depressive disorder report deficits in motivated behavior which are oftentimes accompanied by changes in appetite and weight. Based on a wealth of accruing evidence from animal studies, the investigators suggest that the gut acts as an important arbitrator in effort allocation by signaling the energy level of the body. Within this physiological framework, ghrelin is thought to signal a short-term energy deficit to increase reward responsivity and willingness to work for reward as compensatory (allostatic) means. Here, the investigators propose to conduct a follow-up study (to NCT05318924) with subcutaneous administration of ghrelin vs. saline in patients with major depressive disorder and healthy control participants. During each visit, participants will receive a subcutaneous administration of either ghrelin or saline and perform an effort allocation task where they have to exert physical effort to obtain food and monetary rewards. The investigators hypothesize that ghrelin will increase the motivation to exert effort for rewards. The goal of this follow-up study is to test that the motivational effects of ghrelin are similar in patients with depression and healthy control participants. Furthermore, participants resting energy expenditure will be estimated before and after the administration. In line with a role of ghrelin as an energy deficit signal, the investigators expect ghrelin to decrease energy expenditure. During each visit, participants will answer questions about their current mood and physiological state. The investigators hypothesize that ghrelin increases mood state and hunger while decreasing satiety.

Conditions

Major Depressive Disorder

Keywords

energy homeostasis; motivation; ghrelin; anhedonia; mood

Outcome Measures

Primary Outcomes (4)

• Ghrelin-induced changes in motivation

  Frequency of button presses on a XBox controller to obtain rewards after ghrelin administration vs. saline administration

  15-50 minutes after subcutaneous administration (ghrelin vs. saline)

• Ghrelin-induced changes in Resting Energy Expenditure

  Changes in energy expenditure after a ghrelin administration (vs. saline) as measured with indirect Calorimetry.

  Pre injection versus 50-65 minutes after injection (compared to saline)

• Ghrelin-induced changes in mood

  Changes operationalized via visual analogue ratings (0-100) of the sum score of positive and negative affect schedule mood items after ghrelin administration vs. saline administration. Measures are taken \~40 minutes and 5 minutes prior to injection, as well as 15, 50, and 65 minutes after injection.

  Pre injection timepoints (mean over 40 minutes and 5 minutes before) versus post injection timepoints (mean over 15, 50 and 65 minutes after injection) (compared to saline)

• Ghrelin-induced changes in hunger and satiety from baseline

  Change in visual analogue scale (0-100) measures of subjective hunger and satiety after ghrelin administration vs. saline administration. Measures are taken \~40 minutes and 5 minutes prior to injection, as well as 15, 50, and 65 minutes after injection.

  Pre injection timepoints (mean over 40 minutes and 5 minutes before) versus post injection timepoints (mean over 15, 50 and 65 minutes after injection) (compared to saline)

Study Arms (2)

Major depressive disorder

EXPERIMENTAL

Patients with major depressive disorder will receive a subcutaneous injection of ghrelin (experimental) on one day and saline (placebo) on another day (order randomised; double-blind cross-over design).

Drug: Ghrelin; Drug: Saline

Healthy control participants

EXPERIMENTAL

Healthy control participants will receive a subcutaneous injection of ghrelin (experimental) on one day and saline (placebo) on another day (order randomised; double-blind cross-over design).

Drug: Ghrelin; Drug: Saline

Interventions

Ghrelin DRUG

Participants in this arm will receive a subcutaneous injection of acyl-ghrelin as the active condition.

Also known as: Acyl-ghrelin

Healthy control participants; Major depressive disorder

Saline DRUG

Participants in this arm will receive a subcutaneous injection of saline as placebo control condition.

Also known as: Placebo

Healthy control participants; Major depressive disorder

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \* Must have participated in the behavioral study arm of NCT05120336

You may not qualify if:

• participation in the neuroimaging part of NCT05120336
• breastfeeding
• pregnancy

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

Department of Psychiatry & Psychotherapy, University of Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Anhedonia

Interventions

Ghrelin; acyl-ghrelin; Sodium Chloride

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Nils B Kroemer, PhD

  University of Tübingen, Faculty of Medicine, Department of Psychiatry & Psychotherapy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2024
• First Posted: August 28, 2024
• Study Start: September 2, 2024
• Primary Completion: December 20, 2024
• Study Completion: December 20, 2024
• Last Updated: December 22, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Access Criteria: Until the data is publicly available, researchers may contact the lead PI to gain access

Locations

DE (1)